Language

English

Publication Date

1-1-2024

Journal

Drug Discovery Today

DOI

10.1016/j.drudis.2023.103832

PMID

37977285

PMCID

PMC10872262

PubMedCentral® Posted Date

1-1-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

As a highly contagious human pathogen, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has infected billions of people worldwide with more than 6 million deaths. With several effective vaccines and antiviral drugs now available, the SARS-CoV-2 pandemic been brought under control. However, a new pathogenic coronavirus could emerge in the future, given the zoonotic nature of this virus. Natural evolution and drug-induced mutations of SARS-CoV-2 also require continued efforts for new anti-coronavirus drugs. Nonstructural protein (nsp) 3 of CoVs is a large, multifunctional protein, containing a papain-like protease (PLpro) and a macrodomain (Mac1), which are essential for viral replication. Here, we provide a comprehensive review of the function, structure, and inhibition of SARS-CoV/-CoV-2 PLpro and Mac1. We also discuss advances in, and challenges to, the discovery of drugs against these targets.

Keywords

Humans, SARS-CoV-2, COVID-19, Antiviral Agents, Virus Replication, Drug Discovery, SARS-CoV-2, Papain-like protease, Macrodomain, Inhibitors, Drug discovery

Published Open-Access

yes

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